Epidermis-specific KO of caspase-8. (A) Quantitative assessment of WT and deleted caspase-8 alleles in Casp-8F/−K5-Cre mice by genomic PCR. (B) X-gal staining for β-galactosidase activity in the skins of ROSA26-reporter Casp-8F/+K5-Cre (F/+) and ROSA26-reporter Casp-8F/−K5-Cre (F/−) mice, demonstrating specific Cre-induced recombination in the superficial and follicular epidermis and hair follicles. Bars, 50 µm. (C) General appearance of Casp-8F/+K5-Cre and Casp-8F/−K5-Cre mice at P7. The mutant is much smaller than the WT. The skin is unevenly thickened with marked alopecia and hyperkeratosis. (D) Microscopy of the skin. At P0, the skin of the Casp-8F/−K5-Cre mice is indistinguishable in appearance from the skin of the Casp-8F/+K5-Cre mice. At P7 there is marked epidermal hyperplasia and widespread dermal inflammatory cellular infiltration in the Casp-8F/−K5-Cre mouse. Arrows in B and D point to intraepidermal eosinophilic pustules. H&E; Bars, 50 µm. (E) The affected epidermis contains numerous dyskeratotic foci, consisting of maloriented keratinocytes often forming a whorl around a central keratinocyte which has become prematurely keratinized (arrows). H&E; Bars, 50 µm. The data presented in B, C, D, and E are representative of analyses of 4, 350, 30, and 30 mice, respectively.